Formation of microcapsules, capsules or beads by chitosan was suggested for encapsulation of pharmaceuticals, enzymes, cells, etc. The reported procedures are based on:
A. Using a combination of chitosan, which is a polycationic substance, with a polyanionic substance such as gum Arabic, by a method known as complex coacervation (e.g. JP 87-173464). By this method, an insoluble polymeric shell is produced.
B. Formation of the microcapsules by dispersing an aqueous solution, which contains chitosan, in an oil phase, followed by gelling (e.g. JP 90-317739). This method is based on formation of a separate phase in oil, followed by gellification of the aqueous droplet, and not only the interface.
C. Covalent crosslinking of e.g. beads, by using special cross-linking agents, followed by UV irradiation (e.g. WO 87-US1495).
D. Formation of polymeric spheres by providing droplets of polyanion monomer solution, which meets a stream of polycation monomer solution (e.g. WO (b 92-US9781). This method is based on technology which allows specific contact points between the reactants, and the resulting particle size is controlled by the machinery.
E. Formation of beads, by emulsification of an oil phase directly into a chitosan solution, which is then dropwise added into a solution containing diphosphate and glyoxal hydrate, which leads to crosslinking (e.g. EP 543572). Here, there is no microencapsulation process which occurs at the oil-water interface, but a simple gellification of the whole bead.
As will be shown in the following description, the process of the invention is based on formation of an insoluble wall around each, or only few droplets, in such manner that this wall separates each oil droplet from the aqueous phase.
Formation of biodegradable chitosan-containing aqueous emulsions or sustained release chitosan microcapsules, which have good adhering properties to negatively charged surfaces is desired, and would have a particular advantage for providing natural oil containing biodegradable long-acting lice repelling compositions.
The number of cases of human lice infestation throughout the world is estimated at hundreds of millions each year [Taplin, D. and T. L. Meinking, Sem. Dermatol. (1987) 6:125-135]. The conventional treatment for head lice consists of using synthetic ingredients, which are licidals. However, these chemicals do not solve the problem of reinfestation, which occurs frequently among children. Therefore, the need for a lice repellent is clear.
Insect repellents mostly operate from a distance by confusing the insect's direction finding mechanisms and close up by acting as sensory blockers [Wright, R. H., Sci. Amer. (1975) 233:104-111]. They render the host animal unattractive and in this way protect the host animal from the bites of insects, or ticks and the most pathogenic microorganisms which they transfer. Repellents are normally volatile and consequently remain on the user for a limited period of time.
in the past, lavender oil was used to protect children from head lice infestation [Burgess, I. Br. J. Dermatol. (1993.sup.a) 128:357-358]. Recently piperonal (1,3-benzodioxol-5-carboxaldehyde) was introduced as a repellent to the market [Burgess, I. Pharmaceutical J. (1993.sup.b) 15:674-675], however, it was shown earlier that this substance has also pediculicidal activity [Moore, W. JAMA (1918) 71:530-531].
The U.S. army has for a long time applied the following repellents to clothing, against body lice: M-1960 (30% 2-butyl-2-ethyl 1-3 propanediol, 30% benzyl benzoate, 30% n-butylacetanilidine and 10% TWEEN 80), 90% benzyl benzoate and a combination of 75% N,N-diethyl-m-toluamide (DEET) and 25% ethanol. Pyrethrum has been used to impregnate underwear, and has both a repellent and toxic effect [Eldridge, B. F., In: The control of lice and louse-borne diseases (1973) PAHO/WHO Sci. Pub. No. 263, pp 177-178].
Today the US and Australian armies are using permethrin and di-butylphthalate as a clothing treatment against a number of medically important arthropods, particularly mosquitoes and chiggers [Gubta, R. K. et al., J. Am. Mosq. Control Assn. (1987) 3: 556-560; Frances, S. P. et al., J. Med. Entomol. (1992) 29:907-910].
The repellent DEET, which is widely used against several arthropods of medical importance, exhibits several side-effects including cardiovascular effects, encephalopathies, allergic and psychotic reactions [Robbins, P. J. and M. G. Cherniak, J. Toxicol, Environ, Health (1986) 18:503; Edwards, D. L. and C. E. Johnson, Clin. Pharm. (1987) 6:496-498; Leach, G. J. et al., J. Toxicol. Environ. Health (1988) 25:217].
It is therefore clear why a natural lice repellent composition is required, especially if formulated in such a way that it would yield long duration of lice repellency.
Sustained release preparations of other oily active agents, such as vitamin E or oil-soluble UV radiation photoprotectants has also encountered problems. For example, the optical properties of photoprotectants are required while they stay on the skin. However, the contact between the skin and the photoprotectant is often a problem, due to the chemical composition of the protectant, which might cause allergenic effects, and is in some cases also cause skin deseases.